DT5aP-Hib-IPV and MCC vaccines: preterm infants' response to accelerated immunisation.

AIMS: To describe the immune response of preterm infants to combined diphtheria/tetanus/5 component acellular pertussis-Haemophilus influenzae type b inactivated polio vaccine (DT5aP-Hib-IPV) and meningococcal serogroup C conjugate vaccine (MCC) under accelerated schedule. To compare results with term infants immunised with DT5aP-Hib-IPV and with historical data from preterm infants immunised with a DT3 component aP-Hib vaccine. METHODS: Prospective observational study in preterm infants born at <32 weeks gestation with comparison to contemporary cohort of term infants. DT5aP-Hib-IPV and MCC vaccines were given at 2, 3, and 4 months. RESULTS: Fifty preterm infants (mean gestational age 28.5 weeks) completed the study. After three doses of vaccines Hib polysaccharide IgG geometric mean concentration (GMC) was 1.21 microg/ml with 80% > or =0.15 microg/ml; MCC serum bactericidal assay geometric mean titre (GMT) was 1245 with 100% > or =8. All infants achieved protective titres to diphtheria, tetanus, and the three poliovirus types with > or =80% achieving protective rises in IgG against the five pertussis antigens. CONCLUSION: Preterm infants immunised with DT5aP-Hib-IPV and MCC vaccines show IgG responses to Hib and MCC greater than seen historically in both term and preterm infants with a DT3aP-Hib vaccine, and for pertussis antigens and poliovirus type 1 responses similar to that seen in term infants immunised with DT5aP-Hib-IPV. Responses to poliovirus types 2 and 3 are reduced, but all infants achieved protective titres.

Responses to a fourth dose of Haemophilus influenzae type B conjugate vaccine in early life.

OBJECTIVE: To describe the immune response of preterm infants, with a reduced response to primary Haemophilus influenzae type B (Hib) immunisation, to a fourth dose of Hib conjugate vaccine given in early life. DESIGN: Prospective observational study. SETTING: Five Wessex Neonatal Units. PATIENTS: Infants born at < 32 weeks and immunised with three doses of combined acellular pertussis-Hib vaccine, with a Hib IgG geometric mean concentration (GMC) < 1.0 microg/ml after these primary immunisations. INTERVENTIONS: An additional fourth dose of Hib conjugate vaccine given before 1 year of age. Blood taken to assess Hib IgG concentration and avidity after immunisation. MAIN OUTCOME MEASURES: Hib IgG GMC and avidity index. RESULTS: Ninety six infants (mean gestational age at birth 29.1 weeks) received a fourth dose of Hib at a mean age of 7.8 months. Hib IgG GMC after the primary immunisations was 0.17 microg/ml (95% confidence interval (CI) 0.14 to 0.20) rising to 4.68 microg/ml (95% CI 3.36 to 6.57) after the fourth dose (p < 0.0001). The IgG response to the fourth dose correlated positively with the response after the primary immunisations (p < 0.001). Hib IgG geometric mean avidity index (GMAI) after the primary immunisations was 30.87 (95% CI 20.40 to 46.73). This increased to 124.73 (95% CI 109.93 to 141.51) after the fourth dose (p < 0.0001). CONCLUSION: Preterm infants with very low IgG responses to Hib after primary immunisations with a combined acellular pertussis-Hib vaccine mount a good response to a fourth dose of Hib. This study suggests that all infants will benefit from a fourth dose of Hib, regardless of the age at which it is given.

Acellular pertussis vaccine given by accelerated schedule: response of preterm infants.

OBJECTIVE: To describe the immune response of preterm infants to a diphtheria/tetanus/three component acellular pertussis (DTaP) vaccine, under an accelerated schedule, and the effects of steroids on this response. To compare responses with those of term infants. DESIGN: Prospective observational study. SETTING: Five Wessex neonatal units; Hertfordshire immunisation clinics. PATIENTS: Infants born at < 32 weeks; term controls. INTERVENTIONS: DTaP-Haemophilus influenzae type b vaccine given at 2, 3, and 4 months. Blood taken to assess antibody responses to vaccines. MAIN OUTCOME MEASURES: IgG geometric mean concentrations (GMC) to vaccines. RESULTS: A total of 130 preterm (mean gestational age 29.1 weeks) and 54 term infants were recruited. After the third immunisation, preterm infants had similar GMCs to controls to diphtheria, tetanus, filamentous haemagglutinin (FHA), and pertactin (PRN), but a significantly lower GMC to pertussis toxin (PT). Responses to tetanus and PRN increased with age at the third immunisation, and those to tetanus, FHA, PRN, and PT increased with gestational age at birth. Response to tetanus correlated negatively with the number of doses of antenatal steroids received. There was no association between responses and postnatal steroids. CONCLUSION: When immunised with a combined acellular pertussis- H influenzae type b vaccine under an accelerated schedule, IgG GMC of preterm infants to PT was reduced. GMCs to tetanus, FHA, PRN, and PT increased with gestational age at birth, and GMCs to tetanus and PRN increased with age at the third immunisation. There is, however, no benefit in delaying immunisation. Anti-tetanus IgG decreased with increasing number of doses of antenatal steroids. There was no effect for postnatal steroids.

Immune response of premature infants to meningococcal serogroup C and combined diphtheria-tetanus toxoids-acellular pertussis-Haemophilus influenzae type b conjugate vaccines.

To determine the immune response of premature infants to meningococcal serogroup C capsular polysaccharide (MCC) and combined diphtheria-tetanus toxoids-acellular pertussis-Haemophilus influenzae type b (DTaP-Hib) conjugate vaccines, 105 infants born at <32 weeks' gestation had Hib IgG geometric mean concentrations (GMCs) and MCC serum bactericidal antibody (SBA) geometric mean titers (GMTs) measured 1 month after the third immunization. Term infants served as control subjects. Premature infants had Hib GMCs of 0.27 microg/mL, with 21% achieving GMCs >1.0 microg/mL, compared with 0.81 microg/mL and 46% in term infants (P<.001 and P=.003, respectively). The MCC SBA GMT was 398, with 99% achieving an SBA > or =8, compared with 380 and 98% in term infants (P=.84 and P=1.0, respectively). Hib IgG was associated with age at third immunization (P<.001). When combined with the DTaP vaccine used in this study, the Hib GMC of premature infants was extremely low. The SBA GMT to MCC was similar to that of term infants.

Timing of immunisation of premature infants on the neonatal unit and after discharge to the community.

Premature infants discharged to the community are having their primary immunisations delayed and this delay increases with subsequent doses. The importance and safety of immunising premature infants should be stressed to parents, health visitors, and general practitioners.

Dwarfism, rhizomelic limb shortness, and abnormal face: new short stature syndrome sharing some manifestations with Robinow syndrome.

We describe a child with short stature of prenatal onset, rhizomelic limb shortness affecting the upper limbs particularly, and an unusual face. She had frontal balding, mid-face hypoplasia, a small nose, macrostomia with down-turned corners of the mouth, gingival hypertrophy, and hypoplasia or absence of the clitoris. There was no gross modelling defect of the skeleton and the vertebral column was normal. Some of these manifestations overlap with those of Robinow syndrome.

Evidence for variable gene expression in a large inbred kindred with autosomal recessive spondylocostal dysostosis.

Seven members of a large inbred kindred with autosomal recessive spondylocostal dysostosis were examined clinically, radiographically, and sonographically. The subjects were three adults, one adolescent, and three children under 3 years of age. One child was the offspring of a first cousin marriage which showed quasi-dominant inheritance. Six subjects had short stature owing to widespread vertebral dyssegmentation with variable reduction in rib number and rib fusion. One subject was of normal stature, had limited vertebral dyssegmentation, an extra rib, and no rib fusion. Five subjects showed the plagiocephaly-torticollis sequence. Four of the five male subjects had inguinal herniation on one or both sides. All subjects had normal renal ultrasonography. The youngest subject died of cardiopulmonary complications and is thought to represent one extreme in the expressivity of the gene in this kindred.

Oligohydramnios sequence in a live-born infant following chorionic villus sampling.

We describe an infant born at 29 weeks' gestation with oligohydramnios sequence due to amniotic fluid leakage following chorionic villus sampling at 12 weeks. To our knowledge, this is the first such report.